E-Mail karger@karger.com Original Paper Pharmacology 2015;95:59–64 DOI: 10.1159/000370244 Antinociceptive Synergism of Gabapentin and Nortriptyline in Mice with Partial Sciatic Nerve Ligation Hugo F. Miranda a, b Viviana Noriega a, c Ramiro Zepeda b Pilar Zanetta b Josefina Prieto-Rayo d Juan Carlos Prieto b, c Fernando Sierralta e a School of Pharmacy, Faculty of Medicine, Universidad Andrés Bello, b Pharmacology Program, School of Medicine, ICBM, Faculty of Medicine, c Cardiovascular Department, Clinic Hospital, and d Faculty of Dentistry, Universidad de Chile, and e Dental School, Universidad Finis Terrae, Santiago, Chile showed a synergy in antinociception at a gabapentin-to- nortriptyline ratio of 1: 1 in PSNL mice. This finding suggests that this combination could provide a therapeutic alterna- tive that can be used for neuropathic pain management. © 2015 S. Karger AG, Basel Introduction Neuropathic pain is a type of pain that is distinguish- able from other types because it results from nerve dam- age or dysfunction in either the peripheral or the central nervous system. Neuropathic pain can be induced by au- toimmune disease, metabolic diseases, infection, posther- petic neuralgia, vascular disease, stroke, trauma, and can- cer [1]. Distinct neurophysiological and neurochemical mechanisms contribute to neuropathic pain. Tissue in- jury can trigger the release of pronociceptive mediators that induce a sensitization of the peripheral nerve termi- nals. Modifications of the sensory neurons can also occur Key Words Neuropathic pain · Hot plate test · Hyperalgesia · Isobolographic analysis · Synergy Abstract Background and Methods: Neuropathic pain results from nerve injury, and gabapentin, an antiepileptic drug, has been approved for the treatment of several types of neuro- pathic pain. On the other hand, nortriptyline, an antidepres- sant drug, has been suggested as an alternative treatment. In partial sciatic nerve ligation (PSNL) mice, the interaction of gabapentin with nortriptyline was evaluated by the hot plate assay using isobolographic analysis. Results: Gaba- pentin (3–100 mg/kg, i.p.) or nortriptyline (1–30 mg/kg, i.p.) induced dose-dependent antinociception, with an ED 50 of 11.60 ± 0.54 mg/kg for gabapentin and of 5.16 ± 0.21 mg/kg for nortriptyline. The potency of gabapentin and nortripty- line in PSNL mice at 7 and 14 days after ligation was signifi- cantly increased (p < 0.05). Coadministration of gabapentin with nortriptyline, at a 1: 1 ratio of their ED 50 , had a synergistic effect, with an interaction index of 0.311 and 0.348 for these mice at 7 and 14 days, respectively. Conclusion: The data Received: September 26, 2014 Accepted after revision: December 1, 2014 Published online: January 15, 2015 Hugo F. Miranda Pharmacology Program, School of Medicine ICBM, Faculty of Medicine, Universidad de Chile Independencia 1027, Santiago (Chile) E-Mail hmiranda  @  med.uchile.cl © 2015 S. Karger AG, Basel 0031–7012/15/0952–0059$39.50/0 www.karger.com/pha All authors contributed equally to this study. Downloaded by: Universidad de Chile 198.143.56.33 - 7/28/2015 3:35:12 PM